DHA is the major brain lipid. Recent studies by several groups of investigators have shown that DHA is the parent molecule for a large number of intracellular and extracellular messengers. Chronic perturbation of the pathways regulated by these molecules could account for the subtle behavioral effects seen with neurological diseases. Oxidation of DHA gives rise to a series of non-enzymatically produced analogs of the enzymatically derived products (neuroprostanes) as shown in FIG. 1. Since the structure and chemistries of these neuroprostanes are so similar to the enzymatically-produced compounds, interference in the signal transduction pathways is likely. If the events occur in the brain, one likely outcome is behavioral changes.
Disorders in which measurements of F2-IsoPs has implicated a pathogenic role for oxidative stress include Autism, Alzheimer's disease, Asthma, Huntington's disease, Atherosclerosis, Hepatorenal syndrome, Scleroderma, Cardiac/renal ischemia/reperfusion injury, coronary angioplasty, Se and Vitamin W deficiency, organophosphate poisoning, hyperhomocysteinemia, renal transplant dysfunction, smoking, diabetes, rhabdomyolysis, bile duct obstruction, O2 pulmonary toxicity in premature infants, halothane hepatotoxicity, aceminophen poisoning, age-related decline in renal function, Cr (VI) poisoning, retinopathy of the newborn, alcohol ingestion paraquat poisoning, cisplatin-induced renal dysfunction.
Autism is one of a large family of neurological diseases whose etiology is unknown. It is a neurodevelopmental disorder. Autism is believed to be genetic in origin, with the genetically susceptible being vulnerable to environmental factors. The incidence of Autism is reported to be ˜1:166 and is increasing. The disease is characterized by impaired social interactions, limited verbal and nonverbal communication and repetitive and restricted behavioral patterns. Because patients with Autism exhibit a wide spectrum of symptoms and severity, it is believed that the etiology of the disease is multifactorial.
There is an unsolved problem how to sub-divide the various forms of autism based on biochemical markers rather than clinical observations. One of the reasons why there is so much interest in developing biochemical markers for neurological diseases is that biochemical markers offer the possibilities of both early diagnosis and of devising targeted therapies.
Thus there is a need to be able to track the appearance or disappearance of the non-enzymatically produced products of the oxidation of DHA, and to be able to provide for a missing analog of similar enzymatically produced analogs to prevent or treat the effects of oxidative stress.